Predictors and Prevalence of Nodal Disease in Salvage Oropharyngectomy.

BACKGROUND: Patients with recurrent oropharyngeal cancer often require extensive salvage surgery. For patients with clinically N0 necks, the indication for concurrent neck dissection remains unclear. This study aimed to determine predictors, prevalence, and distribution of nodal disease in patients treated with salvage oropharyngectomy. METHODS: In a case series with data collection at a single tertiary academic National Cancer Institute (NCI)-designated comprehensive cancer center, this study analyzed patients treated with prior radiation or chemoradiation who had persistent, recurrent, or second primary squamous cell carcinoma of the oropharynx requiring oropharyngeal resection between 1998 and 2017 (n = 95). Clinical and oncologic characteristics and treatment outcomes were collected, and statistical analyses were performed. RESULTS: The overall rate of nodal positivity was 21% (24/95), and the rate of occult nodal disease was 6% (4/65). Ipsilateral and contralateral level 2 were the most common areas harboring positive nodes. Bivariate analysis showed female sex (p = 0.01), initial overall stage (p = 0.02), and N status (p = 0.03), as well as recurrent overall and T stage (p = 0.05) to be predictors of nodal disease. In the multivariate analysis, recurrent T stage continued to be significantly predictive of pathologic nodal disease. Both computed tomography (CT) and positron emission tomography-CT were moderately accurate in predicting nodal disease in the salvage setting (area under the curve, 0.79 and 0.80, respectively). CONCLUSION: Occult nodal disease is observed in few patients undergoing salvage oropharyngeal resection. This study identified factors predictive of nodal disease in patients undergoing salvage oropharyngectomy and appropriate diagnostic tests in this setting.

Usefulness of percutaneously injected ethylene-vinyl alcohol copolymer in conjunction with standard endovascular embolization techniques for preoperative devascularization of hypervascular head and neck tumors: technique, initial experience, and correlation with surgical observations.

BACKGROUND AND PURPOSE: Few reports have described the embolization of head and neck lesions by using direct percutaneous techniques. We report our preliminary experience in the direct percutaneous embolization of hypervascular head and neck tumors by using Onyx in conjunction with standard endovascular embolization techniques. We describe the technical aspects of the procedure and its efficacy in reducing intraoperative blood loss. MATERIALS AND METHODS: We retrospectively studied 14 patients (3 females and 11 males; mean age, 33.4 years; range, 11-56 years) with 15 hypervascular tumors of the head and neck that underwent direct percutaneous embolization with Onyx in conjunction with particulate embolization. Nine paragangliomas and 6 JNAs underwent treatment. Documented blood loss was obtained from operative reports in these 15 patients with surgical resection performed 24-48 hours after the embolization. RESULTS: Intratumoral penetration with progressive blood flow stasis was achieved during each injection. A mean of 3.1 needles (20-gauge, 3.5-inch spinal needle) were placed percutaneously into the lesion (range, 1-6). The mean intraoperative blood loss was 780 mL (range, <50-2200 mL). Near total angiographic devascularization was achieved in 13 of 15 tumors. There were no local complications or neurologic deficits from the percutaneous access or embolization of these hypervascular tumors. CONCLUSIONS: In this study, the use of percutaneous injected Onyx in conjunction with standard endovascular embolization techniques in patients with hypervascular head and neck tumors seemed to enhance the ability to devascularize these tumors before operative removal.

Correlation between initial and early follow-up CT perfusion parameters with endoscopic tumor response in patients with advanced squamous cell carcinomas of the oropharynx treated with organ-preservation therapy.

BACKGROUND AND PURPOSE: Current organ-preservation regimens for upper aerodigestive tract squamous cell carcinoma (SCCA) require endoscopic procedures under general anesthesia to evaluate the tumor response. The purpose of our study was to determine whether CT perfusion (CTP) parameters correlate with response to induction chemotherapy as assessed by endoscopy under general anesthesia. METHODS: Nine patients with advanced (stage 3 or 4) SCCA of the oropharynx were enrolled in a nested phase 2 prospective trial in which induction chemotherapy was used to assess the tumor response. Patients underwent direct laryngoscopy and CTP before and 3 weeks after one cycle of induction chemotherapy. The outcome variables were the surgeon's estimate of tumor volume during endoscopy with biopsy under anesthesia and CTP parameters (capillary permeability (CP), blood volume (BV), blood flow (BF), and mean transit time (MTT)). Wilcoxon rank sum analysis was used to correlate the baseline values of BF and BV with response to induction chemotherapy. Comparison of agreement between the reduction in tumor volume and change in CTP parameters was performed by using kappa estimates. RESULTS: Seven of 9 patients demonstrated > or =50% tumor volume reduction, representing positive response to induction chemotherapy. In the responder group, the following changes in mean pre- and postinduction chemotherapy values were noted: mean BF, 114.2 mL/100 g /min (preinduction) to 45.1 mL/100 g/min (postinduction); mean BV, 5.11 mL/100 g to 3.1 mL/100 g; mean CP, 25.6 mL/100 g /min (preinduction) to 18.3 mL/100 g / min (postinduction); mean MTT, 4.9 seconds (preinduction) to 8.0 seconds (postinduction). In the nonresponder group, the following changes were noted: mean BF, 56.9 mL/100 g/min to 75.9 mL/100 g/min; mean, BV 2.7 mL/100 g to 4.71 mL/100 g; mean CP, 24.1 mL/100 g/min to 23.7 mL/100 g/min; mean MTT, 4.3 seconds to 5.34 seconds. Higher baseline (pretherapy) values of BV showed significant correlation with endoscopic tumor response (P < .05). Reduction in the BV (by >/=20%) on follow-up studies also showed substantial agreement with clinical response as assessed with endoscopy (kappa = 0.73). The agreement between decreased BF, decreased CP, and increased MTT and clinical response was fair (kappa = 0.37). CONCLUSION: These preliminary results show that deconvolution-based CTP technique offers potential for noninvasive monitoring of response to induction chemotherapy in patients with oropharyngeal cancers. Percentage reduction of BV is significantly correlated to endoscopic response to induction chemotherapy, though we acknowledge that the data correspond to short-term outcomes and long-term durability of response cannot be established. Nevertheless, validation of the use of deconvolution CTP parameters as predictors of tumor response may permit replacement of an invasive diagnostic procedure conducted under anesthesia currently used to assess response with noninvasive perfusion CT imaging.

Selective cricothyroid muscle reinnervation by muscle-nerve-muscle neurotization.

OBJECTIVE: To determine if selective reinnervation of the cricothyroid muscle could be achieved with muscle-nerve-muscle neurotization. DESIGN: Case series. SETTING: Tertiary referral center. PATIENTS: Three consecutive patients with high vagal lesions that resulted in unilateral laryngeal paralysis. INTERVENTIONS: Patients underwent laryngeal reinnervation with ansa hypoglossi to recurrent laryngeal nerve anastomosis. In addition, patients underwent selective cricothyroid muscle reinnervation by muscle-nerve-muscle neurotization technique. MAIN OUTCOME MEASURES: Objective and subjective improvement in voice quality and electromyographic evidence of selective reinnervation of the cricothyroid muscle. RESULTS: All patients recovered normal or near-normal speaking voice and had normal objective measures of voice quality. They also showed electromyographic evidence of cricothyroid muscle reinnervation. CONCLUSION: The muscle-nerve-muscle neurotization technique was successful in providing selective reinnervation of the cricothyroid muscle in our 3 patients.

Free tissue reconstruction of the hypopharynx after organ preservation therapy: analysis of wound complications.

PURPOSE: Previous series have demonstrated a 77% rate of major wound complications in salvage surgery of the larynx following organ preservation protocols. The purpose of this study is to determine the incidence of wound complications in these patients when microvascular free tissue transfers are used for reconstruction of the hypopharynx. DESIGN: Retrospective case series. SETTING: Academic tertiary care center. PATIENTS AND METHOD: We reviewed the medical records of 42 patients with stage III and IV laryngeal squamous cell carcinoma treated with an organ-sparing protocol consisting of induction chemotherapy followed by definitive radiation therapy. Ten of these patients who required surgical salvage were reconstructed using radial forearm free tissue or lateral arm transfer and constitute the study group. MAIN OUTCOME MEASURES: Wound complications. RESULTS: Wound complications occurred in 2 patients (20%) undergoing free flap reconstruction of the hypopharynx after organ preservation protocols, which was significantly lower (P =.003) than previous reports using other forms of closure and/or reconstruction. One patient in this study group had a small pharyngocutaneous fistula that resolved with conservative therapy after 1 week. The other patient had a larger pharyngocutaneous fistula that resolved over 3 weeks. The mean interval from completion of the chemoradiation regimen to surgery was 21.3 months (range, 2-60 mo). The average free tissue flap size was 94.3 cm(2) (range, 45-165 cm(2)). Average harvest and ischemia times were 59 minutes (range, 41-87 min) and 187.7 minutes (range, 120-240 min), respectively. All flaps survived, and one patient had a minor donor site wound dehiscence. The average hospital stay was 7.8 days. There were no mortalities in this series. CONCLUSIONS: Our results suggest that free tissue transfer reconstruction of the hypopharynx is the preferred method of reconstruction following combined chemotherapy and radiation therapy protocols. Surgical complications are significantly reduced and hospital stays are minimized.

Sentinel node localization in oral cavity and oropharynx squamous cell cancer.

OBJECTIVE: To evaluate the feasibility and predictive ability of the sentinel node localization technique for patients with squamous cell carcinoma of the oral cavity or oropharynx and clinically negative necks. DESIGN: Prospective, efficacy study comparing the histopathologic status of the sentinel node with that of the remaining neck dissection specimen. SETTING: Tertiary referral center. PATIENTS: Patients with T1 or T2 disease and clinically negative necks were eligible for the study. Nine previously untreated patients with oral cavity or oropharyngeal squamous cell carcinoma were enrolled in the study. INTERVENTIONS: Unfiltered technetium Tc 99m sulfur colloid injections of the primary tumor and lymphoscintigraphy were performed on the day before surgery. Intraoperatively, the sentinel node(s) was localized with a gamma probe and removed after tumor resection and before neck dissection. MAIN OUTCOME MEASURES: The primary outcome was the negative predictive value of the histopathologic status of the sentinel node for predicting cervical metastases. RESULTS: Sentinel nodes were identified in 9 previously untreated patients. In 5 patients, there were no positive nodes. In 4 patients, the sentinel nodes were the only histopathologically positive nodes. In previously untreated patients, the sentinel node technique had a negative predictive value of 100% for cervical metastasis. CONCLUSIONS: Our preliminary investigation shows that sentinel node localization is technically feasible in head and neck surgery and is predictive of cervical metastasis. The sentinel node technique has the potential to decrease the number of neck dissections performed in clinically negative necks, thus reducing the associated morbidity for patients in this group.

Conformal re-irradiation of recurrent and new primary head-and-neck cancer.

PURPOSE: To review the outcome of head-and-neck cancer patients re-irradiated using conformal radiation. PATIENTS AND METHODS: From 1983 to 1999, 60 patients with recurrent or new primary head-and-neck cancer received re-irradiation at the University of Michigan. Twenty patients were excluded due to the planned cumulative radiation dose being less than 100 Gy (18) and absence of prior radiation details (2), leaving 40 patients. Thirty-five patients were re-irradiated for unresectable disease, while 4 patients received adjuvant re-irradiation for high-risk disease. Thirty-eight patients had recurrences from previously treated cancer (19 regional, 14 local, 5 regional and local), and 2 patients had new primary tumors. The median time from the first course of radiation to re-irradiation was 21 months. Thirty-one patients (78%) were re-irradiated with curative intent, whereas 9 were treated with palliative intent. Re-irradiation was delivered using conformal techniques in the majority of patients and with concurrent chemotherapy in 14 patients. The median re-irradiation dose was 60 Gy. The median cumulative dose received was 121 Gy. Five patients (13%) did not complete their prescribed course of re-irradiation. RESULTS: The median survival following completion of re-irradiation was 12.5 months. The 1- and 2-year actuarial survival rates were 51.1% and 32.6%, respectively. On multivariate analysis, palliative intent of treatment, tumor bulk, and tumor site other than nasopharynx or larynx were associated with worse survival. The patients treated for unresectable disease did no worse than those treated adjuvantly. The median times to relapse-free survival, local-regional recurrence (LRR)-free survival, and ultimate LRR-free survival (allowing for surgical salvage) were 3.9 months, 7.8 months, and 8.7 months, respectively. Seven patients (18%) are presently alive with no evidence of disease, with a median follow-up of 49.9 months (range 3.3-78.9). Severe radiation-induced complications were seen in 7 patients (18%). Two other patients developed orocutaneous fistulas in the presence of tumor recurrence. Moderate fibrosis and trismus were common. CONCLUSION: Despite the use of conformal techniques, the prognosis of patients treated with re-irradiation is poor, and complications are not infrequent. A subset of patients is salvageable, and high-dose re-irradiation should be considered in selected patients.

Prospective evaluation of eyelid function with gold weight implant and lower eyelid shortening for facial paralysis.

OBJECTIVES: To assess which signs and symptoms were relieved by gold weight implantation and which signs and symptoms persisted. DESIGN: Prospective observational cohort. SETTING: Tertiary care neurotology and oncology center. PATIENTS: Sixteen (4 males and 12 females) consecutive patients whose average age was 56 years (age range, 31-76 years). Inclusion criteria were gold weight implant, lagophthalmos of 2 mm or more, and a House-Brackmann score of 3 or less at the completion of follow-up. Mean follow-up was 13 months. INTERVENTIONS: Each patient received a gold weight implant. Six of these patients underwent a lower eyelid procedure. MAIN OUTCOME MEASURES: Surgical complications, static and dynamic lagophthalmos, static and dynamic corneal coverage, visual acuity, keratitis, topical treatment, and patient satisfaction. RESULTS: There were no extrusions. The preoperative mean lagophthalmos was 7.5 mm and the postoperative mean was 0.5 mm, (P<.001). Corneal coverage with eye closure before implantation was 73% and after implantation was 100%, (P<.001). Corneal coverage with normal (reflex) blink was less than 50% in 9 of 14 patients. When wearing correction, no patients had 20/20 visual acuity. The mean patient satisfaction score before the procedure was 3.5 and after was 7.1, (P<.001). Patient satisfaction was most closely related to visual acuity. The relationship was linear and statistically significant (P<.04). CONCLUSIONS: Gold weight implantation provides significant reduction in lagophthalmos and significant improvement in corneal coverage. But owing to delayed closure time and disrupted tear film, irritation may persist. As a result, some patients require ongoing topical treatment of the eye, which can compromise visual acuity.

Radiation concurrent with gemcitabine for locally advanced head and neck cancer: a phase I trial and intracellular drug incorporation study.

PURPOSE: To examine the feasibility and dose-limiting toxicity (DLT) of once-weekly gemcitabine at doses predicted in preclinical studies to produce radiosensitization, concurrent with a standard course of radiation for locally advanced head and neck cancer. Tumor incorporation of gemcitabine triphosphate (dFdCTP) was measured to assess whether adequate concentrations were achieved at each dose level. PATIENTS AND METHODS: Twenty-nine patients with unresectable head and neck cancer received a course of radiation (70 Gy over 7 weeks, 5 days weekly) concurrent with weekly infusions of low-dose gemcitabine. Tumor biopsies were performed after the first gemcitabine infusion (before radiation started), and the intracellular concentrations of dFdCTP were measured. RESULTS: Severe acute and late mucosal and pharyngeal-related DLT required de-escalation of gemcitabine dose in successive patient cohorts receiving dose levels of 300 mg/m(2)/wk, 150 mg/m(2)/wk, and 50 mg/m(2)/wk. No DLT was observed at 10 mg/m(2)/wk. The rate of endoscopy- and biopsy-assessed complete tumor response was 66% to 87% in the various cohorts. Tumor dFdCTP levels were similar in patients receiving 50 to 300 mg/m(2) (on average, 1.55 pmol/mg, SD 1.15) but were barely or not detectable at 10 mg/m(2). CONCLUSION: A high rate of acute and late mucosa-related DLT and a high rate of complete tumor response were observed in this regimen at the dose levels of 50 to 300 mg/m(2), which also resulted in similar, subcytotoxic intracellular dFdCTP concentrations. These results demonstrate significant tumor and normal tissue radiosensitization by low-dose gemcitabine. Different regimens of combined radiation and gemcitabine should be evaluated, based on newer preclinical data promising an improved therapeutic ratio.

Thyroarytenoid muscle maintains normal contractile force in chronic vocal fold immobility.

BACKGROUND: Denervation of skeletal muscle typically results in irreversible denervation atrophy over time. This finding has generated controversy as to the efficacy of reinnervation procedures for chronic vocal fold immobility related to recurrent laryngeal nerve injury. OBJECTIVE: To test the hypothesis that chronic vocal fold immobility after recurrent laryngeal nerve injury does not result in diminished maximal isometric force generation in the thyroarytenoid muscle. STUDY DESIGN: Adult random-bred cats underwent either unilateral laryngeal denervation (n = 6) or sham surgery (n = 6). After 6 months, videolaryngoscopy was performed followed by in vitro measurement of maximal isometric tetanic force produced by the thyroarytenoid muscle. RESULTS: All animals in the denervation group showed right vocal fold paralysis after the initial denervation operation; none of these animals had return of appropriately phased movement with respiration. Four had intermittent disorganized twitching movements. One had these movements plus an occasional weak adduction, and one had no movement. Normal vocal fold mobility was observed in 6 of 6 animals undergoing sham surgery. The maximal isometric tetanic force measured from the thyroarytenoid muscle in the sham group was 438 mN (+/-92 mN standard deviation [SD]). The maximal isometric tetanic force measured from the thyroarytenoid muscle in the chronically immobile group was 405 mN (+/-107 mN SD). Differences were not statistically significant. CONCLUSION: Maximal isometric force in the thyroarytenoid muscle is not diminished in chronic vocal fold immobility after recurrent laryngeal nerve injury. We conclude that the possibility for restoration of contractile force to the chronically immobile thyroarytenoid muscle exists. This finding supports the pursuit of reinnervation procedures in the treatment of chronic vocal fold immobility.

Pain, quality of life, and spinal accessory nerve status after neck dissection.

OBJECTIVE: To assess quality of life (QOL) in patients with head and neck cancer who underwent neck dissection and to compare QOL scores for patients in whom the spinal accessory nerve (CN XI) was resected or preserved. SETTING AND DESIGN AND OUTCOMES MEASURES: Three hundred ninety-seven patients who had undergone treatment for head and neck cancer completed the University of Michigan Head and Neck Quality of Life (HNQOL) instrument, the Medical Outcomes Study SF-12 General Health Survey, and questions on "pain despite pain medications" and headaches. RESULTS: Of the 397 patients, 222 had no neck dissection, 46 had neck dissections resecting CN XI, and 129 had dissection sparing CN XI. Of the latter group, 68 patients had dissections sparing level V and 61 dissections included level V. Age, sex, primary site distribution, and T stage were not different between the groups. Patients who had neck dissections sparing CN XI had better scores on the HNQOL pain domain (P = .002), had less shoulder or neck pain (P = .003), and took pain medications less frequently (P = .0004) compared with patients who had neck dissections sacrificing CN XI. When CN XI was preserved, patients who had no level V dissection had better pain domain scores (P = .03) and eating domain scores (P = .007) on the HNQOL, had less shoulder or neck pain (P = .006), and had less physical problems (P = .03) than patients who had level V dissected. On multivariate analysis, pain-related QOL scores after neck dissection were significantly better (P < .01) if patients had dissections with preservation of CN XI and if level V was not dissected. CONCLUSION: Neck dissections sparing CN XI are associated with better pain scores on the HNQOL, less shoulder and neck pain, and less need for medications. When CN XI is spared, not dissecting level V of the neck is associated with better HNQOL pain scores, less shoulder or neck pain, and fewer physical problems.

Conformal and intensity modulated irradiation of head and neck cancer: the potential for improved target irradiation, salivary gland function, and quality of life.

PURPOSE: To develop techniques which facilitate sparing of the major salivary glands while adequately treating the targets in patients requiring comprehensive bilateral neck irradiation (RT). PATIENTS AND METHODS: Conformal and static, multisegmental intensity modulated (IMRT) techniques have been developed. The salivary flow rates before and periodically after RT have been measured selectively from each major salivary gland and the residual flows correlated with glands' dose volume histograms. Subjective xerostomia questionnaires have been developed and validated. The pattern of local-regional recurrences has been examined using CT scans at the time of recurrence, transferring the recurrence volumes to the planning CT scans and regenerating the dose distributions at the recurrence sites. RESULTS: Target coverage and dose homogeneity in IMRT treatment plans were found to be significantly better than standard RT plans. Significant parotid gland sparing was achieved. The relationships among dose, irradiated volume and saliva flow rates from the parotid glands were characterized by dose and volume thresholds. A mean dose of 26 Gy was found to be the threshold for stimulated saliva. Subjective xerostomia was significantly reduced in patients irradiated with parotid sparing techniques, compared to patients with similar tumors treated with standard RT. The large majority of recurrences occurred inside high-risk targets. CONCLUSIONS: Tangible gains in salivary gland sparing and target coverage are being achieved and an improvement in some measures of quality of life is suggested by our findings. A mean parotid gland dose of < or = 26 Gy should be a planning objective if significant parotid function preservation is desired. The pattern of recurrence suggests that careful escalation of the dose to targets judged to be at highest risk may improve tumor control.

Anterior ischemic optic neuropathy following neck dissection.

BACKGROUND: Ischemic optic neuropathy (ION) is a rare but devastating complication of surgery. It has traditionally been associated with intraoperative hypotension in patients with underlying arteriosclerosis. METHODS: We present a case of ION following bilateral neck dissections in which there was minimal intraoperative hypotension and preservation of both internal jugular veins. The potential etiology of this disease is discussed along with a review of the literature. RESULTS: Five cases of ION following neck dissection have been documented. This complication is associated with the combination of intraoperative hypotension and anemia in the setting of prolonged bilateral neck dissection. Treatment is supportive, and final visual prognosis is variable. CONCLUSIONS: Ischemic optic neuropathy following neck dissection is best avoided by intraoperative blood pressure and anemia management. When it does occur, supportive therapy must be given. Final visual outcome is variable.

Phrenic nerve reinnervation of the cat's larynx: a new technique with proven success.

Reinnervation of the posterior cricoarytenoid muscle (PCA) should provide vocal cord abduction on inspiration, and passive adduction to enable phonation. Previous investigators have shown that reinnervation is possible, but results have not been clinically encouraging. When reinnervation was successful, the question remained whether it was provided by the transplanted nerve or by the ingrowth of adjacent nerves. In this study the phrenic nerve was transplanted directly into the PCA in a series of 12 cats. Fibrin glue was used to overcome nerve trauma and to prevent retraction of the nerve from the PCA. Laryngoscopy, electromyography, and retrograde labeling of the phrenic motoneurons provided evidence of functional reinnervation in 9 cats. Partial or complete failure in the remaining 3 was due to retraction of the nerve from the muscle. These results appear to justify trials of the procedure in humans.